Studies on experimental models of cardiac hypertrophy and abnormal cardiac physiology have shown significant alterations in the properties of cardiac myosin. It is believed that altered enzymatic activity of myosin - a key constituent of the contractile apparatus may lead to altered cardiac contractility, eventually leading to heart failure. Present investigation is aimed at finding whether similar changes occur in the properties of cardiac myosin in humans with cardiac disease. Results of our studies have shown that the properties of human cardiac myosin are affected by aging. These changes include a loss of cysteine (-SH) groups of myosin, increased breakdown of myosin heavy chains and decreased actin-myosin interaction. Myosin will be isolated from the hearts of patients of different age groups, with or without cardiac disease. The myosin will be characterized for primary structure and enzymatic properties. Special attention will be focused on the mechanism leading to altered actin-myosin interaction and in relation to age of the patient. Mechanisms leading to depressed cysteine content and the relationship to observed breakdown of myosin in aging and in hypertrophied myocardium will be explored in detail. Studies related to the control of actin-myosin interaction (and thus contractile properties of myocardium) are in progress. Here special attention will be focused on the thick filament (myosin-linked) regulation and the role of 18,000 m.w. subunit (Lc2) of cardiac myosin.